Device aimed to help researchers understand the immune system's response to injury

A new
microfluidic tool, which can quickly and accurately isolate
neutrophils (the most abundant type of white blood cell) from a small
blood sample in order to understand the immune system's reaction to
traumatic injury, has been developed by a team of scientists led
by Massachusetts General
Hospital.

Before
recent studies, scientists thought neutrophils' role in the body's
defense against injury was to release antimicrobial proteins and
ingest pathogens, which are fairly small parts to play. But now,
research has found that their roles are much more complex. In fact,
neutrophils are vital to chronic and acute inflammation, the immune
system's response to injury.

Researchers
are now looking to study patterns of protein synthesis and gene
expression in neutrophils in order to obtain more information about
the immune response to injury. But isolating the
cells is usually challenging and takes more than two hours.
Neutrophils are sensitive and easily activated, and handling them the
wrong way can cause them to change molecular patterns that the
researchers are trying to study. This process also requires large
blood samples, and even in a large sample, there are very small
amounts of messenger RNA. But the new microfluidic device makes this
entire process easier and faster.

"Neutrophils
are currently garnering a lot of interest from researchers and
clinicians, but collecting and processing them has been a real
challenge," said Kenneth Kotz, PhD, of the MGH Center for
Engineering in Medicine and lead author of the study. "This tool
will allow a new range of studies and diagnostics based on
cell-specific genomic and proteomic signatures."

Kotz
and his team discovered a system that collects neutrophil-rich
samples in less than five minutes, and from microliter-sized blood
sample. Also, the cells are not disturbed by this system. Kotz
accomplished this by redesigning the antibody-based coating and
geometry of the cell-capture module in the device.

"Until
now, it's been logistically impossible to study neutrophils to the
extent we have in this paper," said Kotz. "This technology
- which is much faster and gentler than current approaches to
isolating cells - can be scaled and modified to capture just about
any cell type, and we're working to apply it to other cell-based
assays."

Laboratory
tests showed that the device collected samples successfully, showing
gene patterns and protein activity relative to the activation status
of the cell. But lab tests are not enough; this device needs to be
applied in real-world environments, and that's exactly what Lyle
Moldawer, PhD, of the University
of Florida College of Medicine and coauthor of the study,
did when he tested the device at six different sites. Samples from 26
patients with traumatic injuries were analyzed and showed complex
interactions that triggered shifts of gene expression patterns.

"This
technology has been widely implemented in our 'Glue Grant Program,'
with a major impact," said Ronald Tompkins, MD, ScD - chief of
the MGH Burns Service and study coauthor. "The ability to
capture specific cells in a routine clinical environment rapidly and
accurately offers a possible change in the paradigm of normal
clinical diagnostics."